ventricular assist devices for permanent therapy: current...
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Ventricular Assist Devices for Permanent
Therapy: Current Status and Future
ProspectsProspects
Francis D. Pagani MD PhD
Professor of Cardiac Surgery
University of Michigan
April 28th, 2012
Disclosures
• NHLBI and HeartWare: Contract research REVIVE-IT
Study, National Co-PI
• HeartWare: Contract research ENDURANCE Study,
National Co-PI
Important Perspectives of VAD Therapy
• INTERMACS (Inter-agency Registry for
Mechanically Assisted Circulatory Support)
INTERMACSInteragency Registry of Mechanically Assisted
Circulatory Support
• National Institutes of Health (NIH) –sponsored collaborative database
• Food and Drug Administration (FDA) – approved • Food and Drug Administration (FDA) – approved durable mechanical circulatory support devices
• Mandatory reporting - Centers for Medicare and Medicaid Services regulate reimbursement
• Data entry – June 2006
Important Perspectives of VAD Therapy
• INTERMACS (Inter-agency Registry for
Mechanically Assisted Circulatory Support)
• Definition of durable, long-term mechanical
circulatory support devicescirculatory support devices
Criteria for Durable “Long-term” Mechanical Circulatory
Support (MCS) Designation
• Durable (reliable performance for > 3-5 years)
• Intracorporeal
− requires operative placement or minimally-invasive
techniques
− Device design intended for both:
o Bridge to transplantationo Bridge to transplantation
o Destination therapy
• “Hands free” untethered mobility > 12 hours / day
− distinguishes paracorporeal systems from intracorporeal
systems
− minimize requirement for frequent battery changes
− quiet operation
• Discharge to home capabilities
Important Perspectives of VAD Therapy
• INTERMACS (Inter-agency Registry for
Mechanically Assisted Circulatory Support)
• Definition of durable, long-term mechanical
circulatory support devicescirculatory support devices
• Indications for VAD therapy for long-term use
Current US FDA-Approved Indications for
Long-term MCS Therapy
• Bridge to Transplantation
– listed for heart transplantation
– Advanced heart failure at risk of imminent death
– Failing optimal medical management
• Destination Therapy (Permanent use of devices as an alternative
to heart transplantation)to heart transplantation)
– persistent NYHA class IV symptoms for 45 of the previous 60
days with optimal medical management
– left ventricular ejection fraction < 25%
– peak oxygen consumption <14 mL · kg1 · min1 or dependent on
inotropes for at least 14 days or IABP for at least 7 days if unable
to exercise
– not a candidate for heart transplantation
Bridge to Bridge to DestinationDestinationBridge toBridge to
Indications for Long-term VAD Therapy
Bridge to Bridge to
TransplantTransplant
DestinationDestination
TherapyTherapy
Bridge toBridge to
CandidacyCandidacy
Indications for Long-term VAD Therapy
• Evaluation for transplantation is a dynamic process
• Patients change transplant status frequently following VAD therapy
• Resolution of relative contraindications
– Pulmonary hypertension– Pulmonary hypertension
– Renal insufficiency
– Debilitation / Frailty
• Occurrence of new contraindications or patient preference
– Elevated panel reactive antibodies
– Stroke
INTERMACS
Implant Year Implant Year
Device strategyDevice strategy
20062006
No. (%)No. (%)
20072007
No. (%No. (%
20082008
No. (%)No. (%)
20092009
No. (%)No. (%)
20102010
No. (%)No. (%)
20112011
No. (%)No. (%) TotalTotal
Bridge to Bridge to
recoveryrecovery
4(3.9)4(3.9) 14(4.0)14(4.0) 15(2.0)15(2.0) 12(1.2)12(1.2) 12(0.8)12(0.8) 15(0.9)15(0.9) 7272
Primary Device Strategy by Year of Implant: June 23, 2006,to Dec 31, 2011a Patient currently listed for transplantb Patient definitely not eligible for transplant
recoveryrecovery
Bridge to Bridge to
transplanttransplantaa
45(43.7)45(43.7) 148(42.6)148(42.6) 367(49.4)367(49.4) 491(49.4)491(49.4) 463(28.9)463(28.9) 370(22.8)370(22.8) 18841884
Bridge to Bridge to
transplant transplant
candidacycandidacy
36(35.0)36(35.0) 132(38.0)132(38.0) 302(40.6)302(40.6) 433(43.6)433(43.6) 598(37.4)598(37.4) 600(37.0)600(37.0) 21012101
Destination Destination
therapytherapybb
16(15.6)16(15.6) 47(13.5)47(13.5) 47(6.3)47(6.3) 47(4.7)47(4.7) 511(31.9)511(31.9) 620(38.3)620(38.3) 12881288
Rescue therapyRescue therapy 2(1.9)2(1.9) 6(1.7)6(1.7) 12(1.6)12(1.6) 5(0.5)5(0.5) 8(0.5)8(0.5) 5(0.3)5(0.3) 3838
OtherOther 0(0.00)0(0.00) 0(0.00)0(0.00) 0(0.00)0(0.00) 5(0.5)5(0.5) 9(0.6)9(0.6) 10(0.6)10(0.6) 2424
TotalTotal 103103 347347 743743 993993 16141614 16201620 54075407
INTERMACS
INTERMACSBridge to Transplant
Transplant - 42% at 1 year
Bridge to Candidacy
Transplant - 26% at 1 year
Destination Therapy
Transplant - 3% at 1 year
Important Perspectives of VAD Therapy
• INTERMACS (Inter-agency Registry for
Mechanically Assisted Circulatory Support)
• Definition of durable, long-term mechanical
circulatory support devices
• Indications for VAD therapy for long-term use• Indications for VAD therapy for long-term use
• Selection of patients with less acuity of illness
INTERMACS Patient Profiles
Kirklin JK, Naftel DC, Kormos RL, et al. Second INTERMACS annual report: more than 1000 primary LVAD implants. J Heart Lung Transplant
2010;29:1–10.
INTERMACS Patient Profiles
INTERMACS
Profiles
NYHA
classifications
Class III Class IIIb/IV Class IV
AHA/ACC
classification
Stage C Stage D
1234567
ApprovedRange of DT Approval and CMS Coverage
Less Sick Sick
INTERMACS 4: Resting symptoms
on oral therapy at home
Not Broadly Accepted Generally Accepted
Ambulatory Class IIIB and IV
INTERMACS 5: Exertion
intolerant
INTERMACS 6: Walking
Wounded
INTERMACS
Kirklin JK, Naftel DC, Kormos RL, et al. Second INTERMACS annual report: more than 1000 primary LVAD implants. J Heart Lung Transplant
2010;29:1–10.
INTERMACS
Patient Selection
Important Perspectives of VAD Therapy
• INTERMACS (Inter-agency Registry for
Mechanically Assisted Circulatory Support)
• Definition of durable, long-term mechanical
circulatory support devices.
• Indications for VAD therapy for long-term use.• Indications for VAD therapy for long-term use.
• Selection of patients with less acuity of illness.
• Superiority of Continuous Flow over Pulsatile
Flow technology.
HeartMate VEHeartMate VE
Thoratec pVADThoratec pVAD
NovacorNovacor
First Generation Pulsatile Volume First Generation Pulsatile Volume
Displacement PumpsDisplacement Pumps
Long-Term MCS Devices• Pulsatile devices 1994 to 2005
• Implantable devices approved for BTT 1998
• REMATCH Trial 2001 – Destination Therapy indication in
2002
History of Destination TherapyREMATCH Trial
22
NEJM 2001;345(20):1435-43.
History of DT – REMATCH Trial
� Randomized clinical trial
– optimal medical therapy
vs. pulsatile flow LVAD
� Non-transplant candidates (n=129)
– EF ≤ 25%,
23
– EF ≤ 25%,
– peak VO2 < 12
ml/kg/min,
– or continuous infusion
inotropes
� FDA approval for HM I (XVE) as destination therapy
NEJM 2001;345(20):1435-43.
Continuous Flow Rotary Pump
Advantages
• No heart valves
• No flexible diaphragm
• No large housing to accommodate pump “stroke volume”
• Fewer moving parts
• Potential for biventricular application
Disadvantages
• Minimal pulse
• Significant AI if pump malfunction occurs
• Operated in fixed mode speed may limit cardiac output
• Afterload dependent
Miller, Pagani, Russell, et. al. NEJM August 2007
Volume Displacement vs. Continuous Flow Rotary
Pumps
• Volume displacement pumps
– Pulsed (“physiologic”) flow based on device function of positive displacement
– VAD flow = beat rate x stroke volume
-5
0
5
10
15
20
25
30
Outflow (L/min)
• CF pumps
– Pump flow follows native cardiac pulse
– Flow increases and decreases in response to LV pressure
– Sensitive to pressure differential across the pump (PAortic- PLV)
– Pump flow determined by pump speed and power
-10
-5
Pump s p e e d = 1 0 ,0 0 0 RPM
-1 0
-5
0
5
1 0
1 5
2 0
2 5
3 0
Outflow (L/m
in)
Both have average flow
between 4-5 L/min
Continuous Flow Rotary Pumps• Flow:
– Directly proportional to rotor speed
– Inversely proportional to pressure ∆ across inlet and outlet
orifices
represents ventricular diastole
represents ventricular systole
Flow Variability
Pulsatile versus Continuous Flow PumpsSuperiority of CF Pumps
Primary Endpoint
50
60
Percent of Patients
Survival at 24 months, free from disabling stroke
or re-operation for device replacement (intention-to-treat)
Primary Composite Endpoint
(% of Patients)
P<0.00162/134 (46%)
0
10
20
30
40
50
Percent of Patients
CF LVAD PF LVAD
29
7/66 (11%)
NEJM 2009;361(23):2241-51.
Adverse Event Profile:
Continuous Flow versus Pulsatile Pump
Mechanical reliability
Infection
RV Failure
Adverse Event Profile:
Continuous Flow versus Pulsatile Pump
Stroke
BleedingBleeding
INTERMACS
Survival for Pulsatile vs Continuous Flow
INTERMACS
600
800
1000
1200
1400
1600
1800
Pulsatile Flow Intracorporeal LVAD Pump (+/- RVAD)
Continuous Flow Intracorporeal LVAD Pump (+/- RVAD)
Pulsatile Flow Paracorporeal LVAD Pump (+/- RVAD)
Pulsatile Flow Intracorporeal TAH
0
200
400
600
2006 2007 2008 2009 2010 2011
Cont Intra Pump 1 1 464 843 1526 1548
Puls Intra TAH 2 22 22 24 27 15
Puls Intra Pump 82 263 183 55 12 2
Puls Para Pump 18 61 74 71 36 55
Adoption of CF Pump Technology
Paradigm Shift
• Obvious and clear benefits of CF over PF technology
• Improvement in survival
• Significant technical advantages at implant due to size
• Reduction in major adverse events:• Reduction in major adverse events:
– Pump replacement / mechanical malfunction
– Infection
– Lower incidence of right heart failure
Ventricular Assist Device Innovation
1st Generation
3rd Generation
2nd GenerationPulsatile Technology
Continuous Flow Technology
Axial Design
Continuous Flow Technology
Centrifugal Design
o Minaturization
o Durability
FDA Approved
BTT 1998
DT 2002
FDA Approved
BTT 2008
DT 2010
Investigational
PMA pending
Bearings
Bearings with stator
Bearingless with
magnetic and
hydrodynamic levitation
Continuous Flow LVAD with Centrifugal Design
• HVAD miniaturized implantable blood pump
• About the size of a “D” battery
• Provides up to 10 L/min of flow
• Centrifugal design, continuous flow
• Hybrid magnetic / hydrodynamic impeller
suspension
• Optimizes flow, pump surface washing, and
hemocompatibility
• Thin (4.2 mm), flexible driveline with fatigue
resistant cables
• Lightweight patient peripherals
HM II Post-Approval Study Starling JACC 2011HVAD BTT Aaronson AHA 2010
HM II BTT Pagani JACC 2009
Axial versus Centrifugal Technology
Improvement in Patient Survival
HM VE DT LVAD REMATCH Rose NEJM 2001
Novacor DT LVAD INTrEPID Rogers JACC 2001
Continuous Flow Rotary Pumps with
Centrifugal Design
• Impeller levitation
– Magnetic coupling
• Active (electrical current)
• Passive (rare earth magnet)
– Hydrodynamic
Rotor
Stator
• Fluid forces
– Hybrid
• Combination of passive or active magnetic coupling with or without hydrodynamic assistance
Centrifugal Technology
• Hydrodynamic performance
– Flat pressure-flow response curve
– Greater safety margin from “suction events”
• Non-contact bearing design
– Larger gaps between impellor and device housing
– Shear stress (importance of transit time –exposure – Shear stress (importance of transit time –exposure to device)
• Blood – Device interface
• Improved flow estimation
• Increased sensitivity to afterload
Ventricular Assist Device Innovation
● Continued miniaturization
● Feasibility of BiVAD or TAH applications due to small size
● Miniaturization of external components with telemetry / remote monitoring capabilitiesMiniaturization of external components with telemetry / remote monitoring capabilities
● Totally-implantable systems
● Minimally-invasive implantation capabilities
● Remote energy transfer systems
● Partial support devices
● Thoratec HeartMate III
─ Centrifugal flow pump design with magnetic levitation of
impellor
● HeartWare MVAD
─ Axial flow pump design with hydromagnetic
levitation of impellor
Ventricular Assist Device Innovation
New Devices in Clinical Trials 2012-2015
● Terumo DuraHeart II
─ Centrifugal flow pump design with magnetic levitation of
impellor
levitation of impellor
● HeartMate X
─ Axial flow pump design with advanced bearing
support of impellor
Summary
• Rapid adoption of continuous flow technology in the
US.
• Superior survival with continuous flow technology
compared to pulsatile technology.
• Destination therapy is becoming the largest • Destination therapy is becoming the largest
indication for device use.
• Inferior survival with use of MCS in Profile 1 – Critical
cardiogenic shock and Profile 2 – Rapid decline.
Conclusions
• Improvements in device technology have led to
superior patient outcomes and greater adoption
of MCS therapy.
• Further expansion of MCS therapy into a less ill • Further expansion of MCS therapy into a less ill
population of patients with advanced heart will
require ongoing technology improvements.
• END
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